Study On Preparation Technology Of Crosslinked Cyclodextrin Inclusion Compound Of Zedoary Turmeric Oil

Zedoary Turmeric oil (ZTO) is extracted from Zedoary Rhizome by stream distillation. Pharmaceutical researches show that it can anti-tumor, anti-inflammatory anti-virus, anti-oxidation, anti-thrombotic and so on. Once the ZTO glucose injection was widely used for anti-virus drug on clinic. But because of the toxicity and stability, China Pharmacopoeia (edition 2010) cancel the embody of ZTO glucose injection. Thus, it’s an urgent problem for us to develop new formulations of ZTO. In this study, we use CDP as carrier and EPI as cross linking agent to prepare ZTO-CDP freeze dried powder which can provide an experimental evidence for clinical use of antiviral agents.1 Formulation① We produce CDP with p-CD and cross-linking agent EPI. Use UV, SEM, DSC, FTIR to confirm the formulation of CDP.② Investigate all kinds of factors such as CDP content, mixing temperature, mixing time, mixing speed and so on in the inclusion process.③ A HPLC method was established by using Curcumol and Germacrone as the index components and methodological investigation was carried out to evaluate the method. The results of HPLC showed that the peak area of Curcumol and Germacrone had a good linear relationship. The regression equation of Curcumol and Germacrone were Y=16420X-21948, R2=0.9990 and Y=70501X-10036, R2=0.9993 respectively. The specificity, precision and stability all meet the requirement which showed that the HPLC method can be used to determine the content of the inclusion complexes.④ Orthogonal design was carried out using these four factors to find that the optimum was CDP content 1 g, inclusion time 4 min, stirring temperature 25℃, stirring speed 300 r/min and alcohol content 2%(mass ratio).2 Lyophilization process⑤ We determine the drying method from vacuum drying, freeze drying, and rotary evaporation drying by using appearance, hydration speed and leakage rate as test materials. The results showed that, we can get pure white inclusion complexes which had a faster rehydration speed from vacuum freeze drying.⑥ Single analysis experiments were carried out to determine the best kind of lyoprotectant was sucrose.⑦ Orthogonal design was carried out using leakage rate as indexes and four factors:content of lyoprotectant, pre-freezing temperatures, pre-freeze time and drying time as test materials. The results showed that the best vacuum freeze-drying process were protective agent sucrose with 3%content,9 h pre-freeze time,10 mm of the thickness and 48 h drying time.3 Quality Inspection① Use SEM、 TLC、FTIR、DSC and XRD to characterize the phases of ZTO-CDP lyophilized powder to verify the formation of the inclusion complexes. The results indicated that the ZTO-CDP lyophilized powder was significantly different from the blank CDP, which can be used to confirm the formulation.② Research the solubility according to the legend items of the solubility determination in China Pharmacopoeia (version 2010) in different media of the lyophilized powder was determined. The ZTO-CDP has good solubility in distilled water, artificial gastric juice and artificial intestinal fluid but almost insoluble in methanol, ethanol.③ Melting range was also detected. The melting range of CDP was 297-313℃. After the freeze-dried powder was made the melting range reduce to 290-303℃.④ The stability of the ZTO-CDP lyophilized powder was detected by putting them under the condition of illumination, high temperature and high humidity. The results showed that ZTO-CDP has good stability under illumination and high temperature. The lyophilized powder becomes toughness and agglomeration at high humidity condition which indicated that we should try to keep dry at the procedure of preparation storage and transport of ZTO-CDP lyophilized powder.In this study, we prepare ZTO-CDP lyophilized powder successfully and study the preparation process and related properties. The results showed that:the preparation technology of the freeze-dried powder is feasible and can be used to solidify ZTO-CDP. The lyophilized powder can significantly improve the solubility and the stability of the drug which can contribute to further development of the new formulations of Zedoary Turmeric oil.